miR‑18a‑5p promotes melanoma cell proliferation and inhibits apoptosis and autophagy by targeting EPHA7 signaling

Mol Med Rep. 2021 Jan;23(1):79. doi: 10.3892/mmr.2020.11717. Epub 2020 Nov 25.

Abstract

Micro (mi)RNAs serve crucial roles in cancer development although little is known about their cellular mechanisms in the pathogenesis of melanoma. The present study explored the regulatory roles of miR‑18a‑5p in melanoma cell proliferation, apoptosis and autophagy, in addition to its target gene in melanoma cells. miRNA and ephrin receptor A7 (EPHA7) mRNA were analyzed by reverse transcription‑quantitative PCR. Cell Counting Kit‑8 and colony formation assays were performed to examine the cell proliferation rate. Hoechst staining and flow cytometry were performed to investigate cell apoptosis. Western blotting was used to estimate the abundance of proteins. Dual-luciferase reporter assay verified the binding of miRNA with target gene sequences. Melanoma tissues and cell lines exhibited markedly elevated miR‑18a‑5p expression. miR‑18a‑5p inhibitor inhibited proliferation rates, and triggered apoptosis and autophagy marker protein expression in WM266‑4 and A375 cells. It also negatively regulated EPHA7 expression in WM266‑4 and A375 cells by directly binding at the 3'‑untranslated region of EPHA7. miR‑18a‑5p mimics reversed the EPHA7 overexpression‑induced suppression of proliferation, and the EPHA7 overexpression‑induced promotion of apoptosis and autophagy. miR‑18a‑5p triggered proliferation of melanoma cells and inhibited apoptosis and autophagy by directly targeting and inhibiting EPHA7 expression. Thus, the present study aided our understanding of miRNA‑mediated melanoma pathogenesis.

Keywords: miR‑18a‑5p; ephrin receptor A7; melanoma; proliferation; apoptosis; autophagy.

MeSH terms

  • Apoptosis*
  • Autophagy*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Female
  • Humans
  • Male
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism*
  • Receptor, EphA7 / genetics
  • Receptor, EphA7 / metabolism*
  • Signal Transduction*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / pathology

Substances

  • MIRN18A microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Receptor, EphA7